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ALCOHOLS,THIOLS,PHENOLS,ETHERS
Severalnewfunctionalgroupsarepresentedinthischapter.Allofthe
functions are based on oxygen and sulfur in the sp hybridized state. The
functional groups contain two pairs of nonbonding electrons and are the
cornerstone of many organic processes. The structures for alcohols, phenols,
thiols,ethersandthioethersareshownbelow.
AlkylOHPhOH AlkylSH
alcoholphenol
thiol
RORRSR
etherthioether
7.1Alcohols
7.1aNomenclature
Prioritiesinnomenclature
Severalfunctionalgroupshavebeenencounteredaswehaveadvanced
throughthechapters.Whenanewfunctionalgroupispresented,itsnomenclature
isalwaysbasedontheparentnamewithanendingthatdesignatesthefunctional
group.Whenseveralfunctionalgroupsarepresentinamolecule,priorityrules
mustbeusedtodeterminewhichfunctionistheparentsystemthatdeterminesthe
numberingofthesystemandthesuffixusedinthefinalname.
Theprioritylistisasfollows:
carboxylicacids>aldehydes>ketones>alcohols>amines>alkene>
alkyne>alkyl,halogen,nitro
Thusacompoundthatcontainedhydroxy,alkeneandketonefunctions
wouldbenamedasaketonewiththeketonegettingthelowestnumberpossible,
andsubstituentsarenumberedaccordinglyandnamedinalphabeticalorder.
Belowthecompoundontheleftisnamedasanalcohol,buttheoneonthe
rightisnamedasaketoneeventhoughbothcompoundshavethesevencarbon
backbone.
124Ch7Alcohols,Thiols,Phenols,Ethers
OH
OH
Cl
Cl
O
7chloro3hepten2ol
1chloro6hydroxy4hepten3one
OHhaspriority
ketonehaspriority
AlcoholNomenclature
Hydroxycompoundsareencounteredfrequentlyinorganicchemistryand
theOHfunctionisofhighprioritywithonlyacids,aldehydesandketoneshaving
higherpriority.Thusmanycompoundshavethealcoholparentsystem.
TheIUPACsystemnamesthelongestchainhydrocarbonastheparent,
dropstheendingeandaddsanewendingofol.Thealcoholhasahigherpriority
innomenclaturethanalkenes,alkynes,alkylgroupsandhalogenandisgivena
numberlowerthananyofthosegroups.Oncetheparentcompoundisidentified
andthelocationofthealcoholfunctionisspecified,otherfunctionsarenamedin
alphabeticalorder.
TheIUPACandcommonnamesforseveralalcoholsaregivenbelow.
Structure
CH3OH
Common
methylalcohol
IUPAC
methanol
CH3CH2OH
ethylalcohol
ethanol
CH3CH2CH2OH
npropylalcohol
1propanol
CH3
CHCH3
isopropylalcohol
2propanol
CH3
tertbutylalcohol
2methyl2propanol
OH
CH3
COH
CH3
7.2Thiols125
CH3CH2CH2CH2OH
nbutylalcohol
1butanol
CH3
CHCH2CH3
OH
secbutylalcohol
2butanol
CH3
CHCH2OH
isobutylalcohol
3methyl1propanol
CH3
cyclohexylalcohol cyclohexanol
OH
benzylalcohol
CH2OH
phenylmethanol
Whenmorethanonehydroxylgroupispresent,theIUPACsystemuses
numberstodesignatethelocationofthehydroxylsalongwithaprefixdi,tri,to
denotethenumberofhydroxyls.Somesystemswithmorethanonehydroxylhave
commonnamesasshown.
OH
CH2 CH2
OH OH
1,2ethandiol
CH2 CHCH2
OHOH
1,2,3propantriol
ethyleneglycol
HOOH
1,2cyclohexandiol
glycerol
'
RCH2OH
RCHOH
R
RCOH
primary
secondary
tertiary
R''
7.1bPhysicalPropertiesofAlcohols
Manyofthephysicalpropertiesofalcoholsaredirectlyrelatedtothe
hydrogenbondingexhibitedbythehydroxylgroup.Inpurealcoholsystems,extra
126Ch7Alcohols,Thiols,Phenols,Ethers
energymustbeaddedinordertocausethesampletoboil,thushighboilingpoints
areobserved.Also,alcoholsformhydrogenbondswith
waterandasaresultareverysolubleinwaterunless
morethansixcarbonatomsarepresent.
H
R
OH OR
becauseofthehydrogenbonding.
CH3OH
CH3CH3
0
CH3CH2CH2CH2OH
o
97
CH3CH2CH3
42
CH3CH2CH2OH
o
78
65
88
CH3CH2OH
118
CH3CH2CH2CH3
0.5
CH3CH2CH2CH2CH3
0
35
Hydrogenbondingisexceptionallyimportantinbiologicalfunction.Many
moleculesthatareactiveinbiologicalprocesseshavetheOHfunctionpresent.
When the molecule is in a living system it must interact with a protein. The
interactionmusthaveaspecificfitastotheshapeandstereochemistryoftheprotein
andthemolecule,andmuchoftheintermolecularattractioncomesfromhydrogen
bondingfromthehydroxylsofthemoleculetooxygenandnitrogensitespresent
in the protein as shown below for pyridoxine, vitamin B 6 interacting with a
proteinreceptor.
proteinreceptor
OH
Pyridoxine
HO
CH3
OH
N
VitaminB6
(grains,milk,eggs)
7.2Thiols
127
7.1cNaturallyOccurringAlcohols
TheROHfunctionistrulyabundantinnature.Allcarbohydrates,also
calledsugars,arecompoundsthatcontainthealcoholfunction.Afewcommon
compoundsarelistedbelow.Bothcitronellolandgeraniolarefoundinplantsand
trees and belong to a family of compounds called terpenes. They are usedas
blends in perfumes and spices. Citronellol is used in candles to help repel
mosquitoes.Mesoinisotol,acarbohydrate,isacompoundfoundinfoodsources
andisimportantinhealthymetabolism.Theaflavinefoundinblacktea,contains
bothaliphaticandaromatichydroxylfunctionsandetherfunctions.
HO
HO
Geraniol
Citronellol
OH
OH OH
OH
HO
HO
O
OH
OH
theaflavine
fromblacktea
HO
HO
OH
OH
OH
OH
Mesoinositolpossible
cellgrowthfactor
(fruits,vegetables,meats)
7.1dPreparationofAlcohols
128Ch7Alcohols,Thiols,Phenols,Ethers
Severalofthelowmolecularmassalcoholsarepreparedonanindustrial
scalethatproducesmillionsoftons.Thealcoholsare
usedthroughoutthechemicalandacademicworld,
commercially as solvents, as medicinal preparations, and in alcoholic drinks
(ethanol)
Methanol is produced in a special process that involves catalytic
hydrogenationofcarbonmonoxide.Methanolisextremelytoxicandcauses
blindnesswheningested.
ZnO/Cr2O4
CO
H2
hightempandpress
CH3OH
Bothethylalcoholandisopropylalcoholaresynthesizedbyacidcatalyzed
additionofwatertoethyleneandpropylenerespectively.
H3O
CH2=CH2
CH3CH2OH
H3O
CH2=CHCH3
CH3 CHCH3
OH
Ethanolisalsoproducedasasupplementforautofuelsbyfermentationofthe
carbohydratesfoundingrain.Theprocessgivesethanolthatcontains5%waterafter
distillation.Thewaterisremovedbyreactionwithlime,calciumoxide.
GrignardReactionswithCarbonylCompounds
Grignardreagentswereintroducedinthehalogenchapter.Theiruseisso
valuable and general in organic chemistry that their reactions will be shown
throughoutmanychapters.Theexampleshownbelowcouldbeexpandedinto
many variations just by changing the halide and the carbonyl compound.
Variationswithothertypesoforganometalliccompoundsarealsoavailable.
7.2Thiols129
CH3CH2Br+Mg
diethylether
CH3CH2MgBr
ethercomplex
1)CH3CH2MgBr
OH
CH2CH3
2)H3O
TherearemanyexamplesoftheuseofGrignardreactions.Theexample
abovecouldbeexpandedintomanyvariationsjustbychangingthehalideandthe
carbonylcompound.Variationswithothertypesoforganometalliccompoundare
alsoavailable.Thereactionisgiveninmoredetailinchapter8onaldehydesand
ketones.
HydrationofAlkenes
Thereactionsshowntoprepareethanolandisopropylalcoholindustrially
areexamplesofelectrophilicadditionofwatertoanalkene.Thepreparationof
higher molecular weight alcohols by hydration is not as important because
rearrangementsoccurandproductyieldsarereduced.
Oxymercurationdemercurationprovidesalcoholsfromalkenesundermild
conditionswithoutrearrangement.Mercuricacetatereactswiththealkenetoform
acyclicmercuriniumionwithapositivecharge.Waterattackstheintermediate
fromthecarbonwiththehighestpositivecharge,thetertiarycarbonhere,and
fromthebacksideofthemercuryatom.Waterandmercurywillbeantiinan
intermediate product which is not isolated, but it is reacted with sodium
borohydridetoconvertthecarbonmercurybondintoacarbonhydrogenbond.
Thefinalresultistheproductionofthealcoholatthemostsubstitutedcarbonof
thealkene,theMarkovnikovproduct.
Oxymercurationdemercuration
CH
Hg(OAc)2
H2O
H2 O
CH3
+
HgOAc
CH3
HgOAc
OAc
OH
CH
+
3
HgOAc
NaBH4
OH
CH3
130Ch7Alcohols,Thiols,Phenols,Ethers
Alkenesreactwithborane,BH3 ether,bysynadditionofhydrogenand
borontothealkene.Theboronatomaddstotheleastsubstitutedcarbonatom.
After three alkene units have added the intermediate is treated with basic
hydrogen peroxide to form the alcohol. The process is called hydroboration
oxidation.TheprocessprovidesthealcoholwithantiMarkovnikovselectivity.
Hydroborationoxidation
CH3
CH3
BH3
B
H3C
H2O2
OH
CH3
CH3
OH
ReactionsofHaloalkanes
Halogenatedalkanescanbeconvertedtoalcoholsbyreactionsdescribed
inchapter5on NucleophilicSubstitutionandElimination. Themainpointsof
reactions of alkyl halides are that the primary halides react by S N2 and E2
reactions,whilesecondaryandtertiarysubstratesreactprimarilybyS N1,E1and
E2reactions.Resultsareshownforreactionsofprimaryandtertiaryhalideswith
hydroxide,whichisbothagoodnucleophileandstrongbase.
SN 2
E2
CH3CH2Br+ OH
CH
CH3CH2OH +Br
CH3
CH3 CBr+OH
CH3
CH2=C
+ H2O Br
CH3
Reactionsofthesamesubstrateswithwater(orwaterinasolvent),whichis
7.2Thiols131
verynonnucleophilicandnonbasic,showonlySN1andE1processeswiththe
tertiaryhalide.
CH3CH2Br
H2O
CH3
CH3
CH3
NoReaction
CH3
H2O
CBr
CH3 COH
CH3
CH2=C
CH3
CH3
SN1
E1
H2O
Br
ReductionofAcids,Esters,AldehydesandKetones
Thecarbonylgroupofseveralfunctionalgroupsmaybeconvertedtothe
alcohol by reducing agents. The reduction of a carboxylic acid with lithium
aluminumhydrideandthereductionofaketonewithsodiumborohydrideare
shownbelow.Bothreactionsexemplifyverycommonandreliableprocedures.
Thesereactionsaregivenindetailinthealdehydeandketonechapter8.
1)LiAlH4
CH3CH2CH2COOH
CH CH CH CH OH
3
2)H3O
1)NaBH4
O
2)H3O
OxidationofAlkenestoVicinalDiols
Compoundswithhydroxylgroupsonadjacentcarbonsarecalledvicinal
diols.OxidationofalkeneswithcoldKMnO4orOsO4providesoccurswithsyn
additionandprovidescisvicinaldiols.Transvicinaldiolscanbepreparedbyring
openingofanoxirane,athreememberedringcontainingoxygen.
OH
132Ch7Alcohols,Thiols,Phenols,Ethers
OH
KMnO4
cis
cold
OH
OH
OH
trans
OH
7.1eReactionsofAlcohols
Acidicpropertiesofalcohols
The high electronegativity of the oxygen atom in alcohols causes the
oxygentotakeelectronsawayfromthehydrogenatom.TheOHbondispolarized
ROH
RO
H
Theionization constantfortheaboveequilibriumisgivenbyKa=
pK
a15.7
16
CH3CH2OH
17
CF3CH2OH
12.4
OH
10
Theacidicpropertyofalcoholsisimportantasitpermitstheformationof
alcoholatesalts,calledalkoxides.Alkoxidesareusefulbothasstrongbasesandas
goodnucleophilesforSN2reactions.Alkalimetalsandotherverystrongbasescan
beusedtogeneratethealkoxides.
2CH3OH
CH3OH
2Na
NaH
2CH3O
Na
H2
CH3O
Na
H2
7.2Thiols133
ConversionofAlcoholstoAlkylHalides
ReactionwithHydrogenHalides
Aliphaticalcoholsreactwithhydrogenhalidestoproducealkylhalides.
ROH
HX
H2O
RX
X=Cl,Br,I
Themechanismofthereactiondependsonthestructureofthealcohol,but
thefirststepalwaysinvolvesprotonationofthealcoholtoformanoxoniumion.
ROH
ROH2
X
oxoniumion
HX
thenisattackedfromthebacksideinaSN2mannertogive1bromobutane.
HBr
CH3CH2CH2OH
+
CH3CH2CH2OH2
CH3CH2CH2Br
+H2O
Br
Thereactionoftertbutylalcohol,atertiaryalcohol,withHBrgivesthe
oxoniumionfirstalso.Butinthiscase,waterislosttogivethetertbutylcation.
ThecationreactswithBr togivemostlythesubstitutionproductaccompanied
bysomealkeneeliminationproduct.
CH3
CH3
COH
CH3
CH 3+
HBr
CH3C
H2O
OH2
CH3C
CH3
CH
Br
CH3
CH3
CH3
CH2
CBr+
CH3
CH3C
CH3
SN1
E1
134Ch7Alcohols,Thiols,Phenols,Ethers
Thereactionsthatinvolvecarbocationsarethemorecomplicatedbecause
oncethecationisformedmanypossibilitiesexistfor
theirreaction:substitution,elimination,and
rearrangement.
Thereactionof3methyl2butanolwithHClgoesthroughtheoxonium
iontothecarbocation.Butthesecondarycationrearrangestothemorestable
tertiarycation.Theproductarisesfromattackofchlorideonthetertiarycation.
CH3 H
H
CH3
CH3
CH3
HCl
OH
CH3
CH3
H
CH3 H
H2O
CH3
C+
CH3
OH2
CH3 H
C
CH3
2 carbocation
CH3
3 carbocation
CH3 H
Cl
CH3 C
Cl
CH3
Bothalcoholsandhalidescanbeusedforgeneratingcarbocations,with
the resulting products depending on reaction conditions. The example below
illustratestheformationofastableallyliccarbocation.
CH3CH=CHCH2Cl
CH3CH=CHCH2OH
HCl
Cl
CH3CHCHCH2
CH3CH=CHCH2Cl
H2O
+
CH3CHCH=CH3
Cl
H2O
CH3CH=CHCH2OH
+
CH3CHCH=CH3
OH
ReactionwithPhosphorusandSulfurHalides
Manyreagentsareknowntoconvertalcoholstohalides.Phosphorus
7.2Thiols135
halidesandthionylchloridearecommonlyusedaswaspresentedinchapter6.
SOCl2
PBr3
Cl
OH
Br
TheMitsunobureactioncanemploythehalideasanucleophiletodisplace
thehydroxylfunctioninaSN2process.Thusthechiralityofthehalideproductis
invertedfromthatofthestartingalcohol.Inthisreactionthehydroxylgroup,whichis
normallyaverypoorleavinggroupasOH ,leaveseasilyasaphosphineoxide.Thus
alcoholsmaybedisplacedintheSN2reactionwithoutbeingconvertedto
anotherfunction(halide,sulfonate)first.
MitsunobuReaction
H
CH3
OH
H3CH2C
CH3
H
Ph3P, KI
EtO2C
Rconfiguration
CO2Et
CH2CH3
SConfiguration
N=N
Dehydration
Whensecondaryandtertiaryalcoholsaretreatedwithacid,acarbocationis
formed.Whenanucleophileispresent,suchashalideintheaboveexample,analkyl
halideisproducedintheSN1process.Butifanucleophileisabsent,thenthe
E1processisfollowedtogiveanalkene.AlcoholsareeasilydehydratedbytheE1
reaction with sulfuric acid. The sulfate formed is too poor to serve as a
nucleophile, thus only elimination is observed. But carbocations are the
intermediatesandthereactionscanbecomplicatedbecauseofrearrangements.
CH3
CHCH3
H2SO4
+OH2
OH
H2O
CH3CHCH3
H
CH
CHCH
CH3CH=CH2
Thedehydrationofthetwomethylcyclohexanolsbelowshowsthatthe
major alkene formed is the most substituted (Saytzeff) product. Also
rearrangementwilloccurtothemoresubstitutedcarbocation.Thusthedifferent
alcoholsgivethesameE1products.
136Ch7Alcohols,Thiols,Phenols,Ethers
CH3
OH
H2SO4
CH3
H2SO4
CH2
major
Saytzeff
minor
CH3
OH
Primary alcohols are not good starting materials for dehydration because
primarycarbocationsarenotgoodintermediates.Reactionofethanolwithsulfuric
acidgivesdiethylether,butdehydrationcanbeachievedwithanaluminacatalystat
hightemperature.
CH3CH2OH
CH3CH2OH
Oxidationofalcohols
H2SO4
150
CH3CH2OCH2CH3
Al2O3,300
CH2=CH2
Twoextremelyvaluablefunctionsinorganicchemistryarethealcoholand
carbonyl groups. The oxidation of alcohols and the reduction of carbonyl
compoundsrepresentsajunctureinwhicheachfunctioncanbepreparedfromthe
other.Anyalcoholthatcontainsandalphahydrogenatomcanbeoxidizedtoa
carbonylcompoundasshown.
HCOH
alcohol
1o
[O]
[H]
[O]
RCH2OH
20
R2CHOH
30
R3COH
C=O
[O]
[O]
carbonyl
[O]
RCH=O
aldehyde
R2C=O ketone
nooxidation
RC=O
OHacid
7.2Thiols137
CH3CH2CH2CH2OH
H2SO4
CH3CH2CH2COOH
Secondaryalcoholsareeasilyconvertedtoketones.Furtheroxidationof
the ketone occurs only under very harsh conditions. The mechanism of the
oxidationinvolvesformationofachromate(VI)esterofthealcoholfollowedby
lossofchromous(IV)acid.
Tertiaryalcoholsdonotpossessanalphahydrogenandcannotbeoxidized,
buttheconditionsofoxidationcansometimescauseE1eliminationreactions.
CH3
CH3
C=O
K2CrO4
HCOH
Mechanism
K CrO
2
4+
CH3
CH3
H2SO4
H2CrO4 +K2SO4
CH3
HCOH+
H2SO4
CH3
H2CrO4
CH3
HCOCrO3H+ H2O
CH3
CH3
CH3
C=O+
H2O+HCOCrO3H
+
H3O
CH 3Cr(VI)
CH3
+
HCrO3
Cr(IV)
138Ch7Alcohols,Thiols,Phenols,Ethers
A solution of CrO3, H2SO4 and acetone, known as Jones reagent, is
commonlyusedinmanyoxidationprocedures.
JonesOxidation
OH
O
CrO3
H2SO4
acetone
Oxidationswithdimethylsulfoxideinthepresenceofaceticanhydrideor
oxalylchloride(Swernoxidation)areespeciallyusefulforconversionofprimary
alcohols to aldehydes without further oxidation to the acid. Pyridinium
chlorochromatealsoservesforthisselectiveoxidation.
O
CH3SCH3
CH2OH
Ac2O
cold
CH=O
ClCrO3
H
Ingested alcohol is oxidized in the liver by an enzyme called alcohol
dehydrogenase. The first product of the oxidation is acetaldehyde which is
responsibleforthewellknown"hangover".Thealdehydeiseventuallyfurther
oxidizedtoacetateandthenontocarbondioxide.
enzyme
CH3CH2OH
7.2Thiols
[O]
CH3CH=O
[O]
CH3 C=O
O
CO2
7.2aNomenclature
Sulfurisonerowdownfromoxygenintheperiodictable.Compoundsthat
containsulfurinsteadofoxygenmightbeexpectedtobearsimilarcharacteristicsof
7.2Thiols139
theoxygencompound.But,thechemistryoftheSHfunctionismuchdifferent
fromtheOHfunction.TheSHgroupiscalledasulfhydrylfunction,butorganic
compoundscontainingtheSHarecalledthiolsintheIUPACsystem,orcalled
mercaptansinoldernomenclature.ThiolnamesintheIUPACsystemarederived
fromtheparentalkanebydroppingtheefollowedbyaddingthiol.Anumberis
usedtolocatethepositionofthethiol.Oldermercaptannamesareobtainedby
namingthealkylgroupfollowedbyasecondword,mercaptan.
SH
CH3SH
methanthiol
thiophenol
methylmercaptan
phenylmercaptan
CH2 CH2
SHSH
CH3CH=CHCH2SH
2buten1thiol
ethandithiol
7.2bPropertiesofThiols
Thiols,unlikealcohols,donotformhydrogenbonds andthereforeare
volatilelowboilingcompounds.Thiolshaveveryunpleasantodors.The2buten
1thiolaboveisoneofthecomponentsofskunkspray.Methanthiolispurposely
addedtobottledgasandnaturalgasinordertorevealleaks.Thiols(pKa=10)are
moreacidicthanalcohols(pKa=16),andtheirprotoncanberemovedbyreaction
withbase.
CH3SH
CH3SNa
NaOH
H 2O
7.2cPreparationandReactionsofThiols
ThiolsarereadilypreparedbytheSN2displacementofhalidesby
sulfhydrylion.Sulfhydrylanionisanextremelygoodnucleophile.
RX
+NaSH
RSH+NaX
X=Cl,Br,I
Thiolsareeasilyoxidizedtodisulfides,andthedisulfidesareeasily
reducedbacktothiols.
CH3CH2SH
I2
NaBH4
CH3CH2SSCH2CH3
disulfide
Theeasyoxidationreductionisimportantinproteinstructure.Keratinisa
140Ch7Alcohols,Thiols,Phenols,Ethers
proteinfoundinhair,anditcontainsthedisulfideunitknownascystine.Hair
treatmentsfirstreducethedisulfidebondandallowthehairtobemanaged.Then
thedisulfidebondsarereformedtokeepthehairinthedesiredshape.
O
O
CHCOH
HOCCHCH2SSCH2
NH2
cystine
reduction
oxidation 2HOCCHCH2SH
NH2
NH2
reduction
CH
CH2
oxidation
CH
SH
2
CH2
HS
Hairnobody
Hairwithbody
7.3Phenols
Phenolsareaclassofcompoundsthatcontainthehydroxylfunctionbonded
to an aromatic ring. Although phenols and alcohols contain the OH group, their
chemistryismuchdifferent.Phenolshaveastronglyacidichydrogen,theCObondis
verydifficulttobreak,andmanyreactionstakeplaceinthearomaticring.
OH
phenol
7.3aNomenclatureofphenols
Thenamesofphenolsarederivedfromoldercommonnames.Thenames
havebeenretainedintheIUPACsystem.Somecommonphenoliccompoundsare
shownbelow.
OH OH
OH
CH3
CH3
ocresolmcresol
pcresol
CH3
7.3Phenols141
OH
OH
OH
OH
OH
catechol
OH
hydroquinone
resorcinol
OH
OH
1naphthol
2naphthol
naphthol
naphthol
7.3bNaturallyOccurringPhenols
Manyphenolsareobtainedbythedistillationofcoal.Vanillin,foundin
vanillabeans,isusedasaflavoringforfood.Salicylicacidisusedtoprepare
aspirin.Resveratrol,foundingrapesandpeanuts,maybeananticanceragent.
Cyanidin,averyabundantcompoundbelongtotheflavoneclassofcompounds,is
responsible for the red coloring in roses. When cyanidin is made basic with
potassiumionsitformsabluecolorfoundinthebluecornflower.
OH
OH
OCH
OH
OH
O
Oglucose
CHO
vanillin
Oglucose
cyanidin
redcolorofroses
142Ch7Alcohols,Thiols,Phenols,Ethers
OH
OH
COO
H
OH
OH
W
resverat
rol
salicylic
acid
7.3c
Reactions
of
Phenols
Phenols
Br2/H2O
Br
Other
electrophilic
substitutionsoccur
readilyundermild
conditionsasseen
arestrongeracids
than alcohols.
belowfornitrationand
OH
acylation.
7.3Phenols143
OH
OH
OH
HNO3
NO2
SiO2
NO2
OH
OH
Ac2O
SnCl4
H3CO
ReductionandOxidation
Cyclohexanolisproducedfromphenolbyreductionwithanickelcatalyst.
Thearomaticringislostinthisprocedure.
OH OH
H2
Ni,heat
pressure
Hydroquinoneissmoothlyoxidizedtothehighlycoloredcompoundknown
asquinone.Quinoneisusedinphotographicprocesses.Thereactionisreversibleand
quinonemaybereconvertedtohydroquinone.Oxidationreductionofthistype
isimportantinbiologicaltransformations.
O
OH
K2CrO4/H
OH
NaBH4
VitaminK,anaturallyoccurringquinonethatplaysaroleinblood
clotting,containsthenaphthoquinonestructureshown.
144Ch7Alcohols,Thiols,Phenols,Ethers
O
CH3
O CH3
CH3
CH
CH3
Phytonadione
VitaminK
(greenvegetables)
Reactionwithfreeradicals
Freeradicalsreacteasilywithphenolstoabstractthehydrogenatomfrom
theOHgroup.Hydroquinoneisveryefficientinreactionswithradicalsthatitis
usedtoterminateorinhibitradicalreactions.Inhibitionofradicalsisimportant
whenfreeradicalsmaybepresentinareactionandcauseundesiredreactions.
Certainethersareknowntoundergofreeradicaloxidationswithoxygentogive
unstableperoxides.Whenthebottleofethercontainingtheperoxideisshaken,the
peroxideexplodes.Additionofaninhibitorsuchashydroquinonetotheether
prevents formation of radicals and peroxides, and the ether remains free of
explosivetendencies.
O2
light
O
HO
OH
+ O
O
Vitamin E contains a phenolic ring in which the OH reacts with free
radicalstoinhibittheirformation.ManypeopletakevitaminEsupplementsto
suppress radical formation in the body because some theories indicate that
biologicalfreeradicalscausecancer.
7.3Phenols145
CH3
OH
CH3
CH3
CH3
CH3
O
CH3
CH
CH3
CH3
R(freeradical)
CH3
CH3
CH3
Tocopherol
VitaminE
(eggs,meats,oils)
O CH
3
CH3
CH
CH3
+RH
7.4Ethers
Ethersarecompoundsthathavetwoorganicgroupsattachedtooxygen.
Thebondsbetweentheorganicgroupsandtheoxygenformanangleof110and
consequentlyareslightlypolar.Thenonbondingelectronsontheoxygenatom
cause ethers to act slightly basic. Ethers are wellknown for their anesthetic
propertiesbuttheypossessotherusefulchemicalpropertiesaswell.Structuresof
twoanestheticethersareshownbelow,butbetteranestheticsarenowinuse.
CH3CH2OCH2CH3 ClCFHCF2OCH2F2
ether
ethrane
diethylether
7.4aNomenclatureofEthers
Ethersarenamedbytreatingeachsideasasubstituentwithanalkylor
arylnamefollowedbythewordether.Theindividualnamesareseparate.
146Ch7
Alcohols,Thiols,Phenols,Ethers
CH3
CH3CH2OCCH3
CH3CH2OCH2CH3
diethylether
oxirane
CH3
methyltertbutylether
O
O
oxetane
oxolane
OCH3
CH3CH2CH2CH2OCH(CH3)2
nbutylisopropylether
O
oxane
methylphenylether
anisole
Complexethersarenamedbyprefixingthebasenameofahydrocarbon
systemwithanalkoxygroup.
CH3OCH2CH2OCH
1,2dimethoxyethane
CyclicethersarenamedbytheIUPACsystemdevelopedforheterocyclic
compounds.Heretheoxinthenamedenotesoxygen.
7.4bPhysicalPropertiesofEthers
Ethers have boiling points similar to the hydrocarbon obtained if the
oxygenisreplacedbyaCH2group.
CH3CH2OCH2CH3
CH3CH2CH2CH2OCH2CH2CH2CH3
o
bp142
bp35
CH3CH2CH2CH2CH3CH3CH2CH2CH2CH2CH2CH2CH2CH3
o
bp36
bp151
Thenonbondingelectronsonalkyletherscauseaslightlybasiccharacter.
Thusweakhydrogenbondsareformedwithwater,andetherslightlydissolvesin
water.Theetheroxygenisprotonatedinthepresenceofstrongacids.
7.4Summary147
HCl
C2H5OC2H5
H2SO4
C2H5 OC2H5
H
Cl
C2H5 OC2H5HSO
Grignardreagentsrequirethepresenceofanether,usuallydiethyletheror
tetrahydrofuran,becausetheetheroxygenformsacomplexwiththemagnesiumin
thereagent.
C2H5OC2H5
C2H5OC2H5
R X Mg
RMgX
C2H5OC2H5
O
18crown6
O
18crown6PotassiumComplex
18crown6
model
148Ch7Alcohols,Thiols,Phenols,Ethers
7.4cPreparationofEthers
Diethyl ether is prepared from ethanol and sulfuric acid. The reaction
involves the SN2 displacement by ethanol on another positively charged
molecule.The OH2isaverygoodleavinggroup.
H2SO4
C2H5OH
+C2H5OH
C2H5OH
C2H5OC2H5+H2O+
TheuseofanalkoxideintheSN2displacementofprimaryhalidesleadsto
etherproducts.TheprocessiscalledtheWilliamsonethersynthesis.The
alkoxideispreparedbyreactingsodiummetalwiththealcohol.
CH3OH
+ Na
+ CH3CH2Br
CH3O
CH3ONa
CH3O
CH3OCH2CH3+
+ Na
Br
UsuallytworoutesarepossibleintheWilliamsonethersynthesis.Therules
ofSN2reactionsmustbefollowedinthattertiaryalkylhalidescannotbeused.
Thusofthetwochoicespossibleforthepreparationoftertbutylmethyl
ether,theroutethatusesmethylbromideisacceptable,buttheuseoftertbutyl
bromidewillonlygiveE2elimination.MTBEisanenvironmentallysafeadditive
togasoline.
SN2
CH2
CH3 CO
E2
CH3
CH3Br
COCH3
CH3
CH3
CH3
CH3 CH2
CH3
CH3 CBr
CH3
CH3O
MTBE
CH3OH
C
CH3
7.4dReactionsofEthers
Oneofthemainfeaturesofethersisthattheyarerelativelyinert,andthus
serveasexcellentsolvents.Hydriodicacidcanbeusedtocleavetheetherbondas
shown.
7.4Summary149
HI
OCH3
OH+
7.4eFormationofHydroperoxides
A major danger in handling ether solvents is the possibility that some
hydroperoxidehasformedinthesolvent,anditcausesthesolventtoexplode
whenhandled.Thereactionoccursbetweenethersandoxygenandiscatalyzedby
light.Diethylether,diisopropyletherandtetrahydrofuranareespeciallyproneto
theformationofhydroperoxides.
OOH
O2
CH3CH2OCH2CH3
CH3CH2O CHCH
OOH
OOH
(CH3)2CHOC(CH3)2
Notallhydroperoxidesareundesired,andsomeareusedasinitiatorsin
freeradicalreactions.Specialcontroloftheirpreparationisnecessary..
7.4fOxiranes(Epoxides)
Ethers contained in a threemembered ring are called oxiranes by the
IUPACrules,butacommonnameforthesystemisepoxide.Theoxiranesystem
ishighlystrainedandthusshowshighreactivity.Thereactionscausetheringto
openandrelievetheinherentstrain.
Preparationofoxiranes
The simplest oxirane is also called ethylene oxide and is prepared by
oxidationofethylenewithoxygen.
O2/Ag2O
CH2=CH2
250
Peroxidereagents,suchmchloroperoxybenzoicacid,canbeusedtooxidize
alkenestooxiranes.Basicsolutionofordinaryhydrogenperoxide,H 2O2,canalso
beusedtoprepareoxiranesfromalkenes.
CH3I
150Ch7Alcohols,Thiols,Phenols,Ethers
HO
O
Cl
O
CH=CH2
Reactionsofepoxides
Bothacidsandbasescausetheringopeningofthehighlystrainedoxirane.
acidreaction
O
ClCH2CH2OH
Cl
basereaction
O
OCH2CH2OCH2CH3
CH3CH2O
H
HOCH2CH2OCH2CH3
Grignardreagents,andorganolithiumreagents,reactwithoxiranetogive,
afterprotonation,analcoholthatistwocarbonslongerthanthestartingGrignard
reagent.
2
CH3CH2MgBr
7.4g
2)H
CH3CH2CH2CH2OH
Thioethers(Sulfides)
Sulfuranalogsofethers,knownasthioethersorsulfidesaremuchless
knownthanthenormaloxygenether.Butseveralimportantcompoundsinthis
familydeservementioning.Mostofthecompoundshaveeitheracommonname
oranamederivedfromnamingthesubstituentsfollowedbythewordsulfide.
7.4Summary151
CH3SCH3
PhSPh
dimethylsufide
S
S
diphenylsulfide
thiolane
thiophene
tetrahydrothiophene
Thioetherssmelljustasterribleasthiols,perhapsworse.Inadditionsome
thioethersinplants,suchasgarlicandonion,contributetothetaste.Garlic,which
hasseveralhelpfulhealthrelatedpropertiesincludingloweringofbloodpressure,
hastwostructuresofsimilarstructure.Allicinisapotentantibacterialagentwhile
allylingivesthecharacteristicbadodorofgarlic.
Allylin
Allicin
Anantibacterialfoundingarlic
Odorofgarlic
ThioethersarepreparedbyaprocedurerelatedtotheWilliamsonether
synthesis.Sulfideanions,whichareexcellentnucleophiles,reactinSN2
displacementofhalidesinalkylhalides.
CH3S ICH2CH3
Br
CH3SCH2CH3
Br
Na2S
Biotin(VitaminH)containsacyclicsulfidering.Biotinisacoenzyme(that
meansitworksinconjunctionwithanenzyme)involvedinthetransferofCO 2in
biologicalreactions.
152Ch7Alcohols,Thiols,Phenols,Ethers
NH NH
OH
S
O
Biotin
VitaminH(egg
yolk,kidney)
CH3SCH3
H2O2
O
CH3SCH3
dimethylsulfoxide
H2O2
O
CH3SCH3
O
dimethylsulfone
Dimethylsulfoxide(DMSO)iswellknowninorganicchemistryforits
abilitytodissolvemanysubstancesincludingsomesalts.Inmedicine,dimethyl
sulfoxideisusedtotreatarthritisasitisadsorbedthroughtheskin.Thusrubbing
affected areas with dilute DMSO solutions gives relief. Some drugs may be
administeredbydissolvinginDMSOandabsorbingthroughtheskin.DMSOhas
afainttasteofoysters.
7.4Summary153
7.5Summary
AnaliphaticorganiccompoundcontaininganOHfunctionistermedan
alcohol.Alcoholsareslightlyacidicandarecapableofformingstronghydrogen
bondsgivingrisetoincreasedboilingpoints.Alcoholsareclassifiedasprimary,
secondaryandtertiary.
Alcoholsarepreparedbyregioandstereoselectivehydrationofalkenes
by oxymercurationdemercuration, hydroborationoxidation, and by direct
hydroxylation.Grignardreactionswithcarbonylcompoundsgivealcohols.
Nucleophilicsubstitutionofprimaryalkylhalideswithhydroxideionproduces
hydroxylic compounds. Reduction of carboxylic acids, aldehydes, esters,
aldehydes and ketones also yields alcohols. Mild oxidation of alkenes with
permanganateorperoxideproducesvicinaldiols.
Alcohols,asmildacids,reactwithalkalimetaltogivealkoxidethatare
usefulbasesandnucleophiles.Alcoholsreactwithhydrogenhalidestoproduce
alkylhalidesinreactionsthatinvolveS N2mechanismforprimaryalcohols,and
SN1andE1mechanismsforsecondaryandtertiaryalcohols.Alkylhalidesare
alsopreparedfromthionylchlorideandphosphorushalidereagents.Alcoholsare
dehydratedwithsulfuricacidinreactionprocessesthatinvolvecarbocations.
Alcoholsareoxidizedwithawidevarietyorreagentstogiveacid,aldehydesand
ketones.
Thiols arerelatedtoalcoholsbyhavingthe sulfhydrylfunction,SH, in
placeofthehydroxylfunction,OH.Butthiolsareverydifferentfromalcoholsin
their properties, most notably possessing foul odors. Conversion of thiols to
disulfidesisanimportantbiologicalprocessinproteinstructure.
Aromaticalcohols,knownasphenols,bearlittleresemblancetoaliphatic
alcohols. Phenols are solids, highly polar, highly acidic, and do not have
reactionsthatbreaktheCObond.Thearomaticringofphenolsisveryreactive
toelectrophilicaromaticsubstitution.Oxidationreductionprocessesthatinvolve
phenolsandquinonesareimportantbiologicaltransformations.
Ethersarerelativelyinert,lowboilingcompoundsusefulassolventsfor
organic reactions. The Williamson ether synthesis is often used in their
preparation.Cyclic,threememberedethers,knownas oxiranesorepoxides are
reactivespeciesusefulinseveralringopeningreactionswithnucleophiles.
154Ch7Alcohols,Thiols,Phenols,Ethers
7.6ProblemSet
7.1ProvideIUPACnamesforthestructuresad,andprovidestructuresforeh.
a)4methyl2pentanol
c)trans4tertbutylcyclohexanol
OH
e)
f)Cl
OH
H3C
Cl
g)
CH(CH3)2
HO
b)4,4,4trifluoro2butanol
d)trans1,2cyclohexandiol
CH3
CH3
CH3 OH
h)
7.2 Classifythealcoholsinproblem7.1asprimary,secondary,tertiary,allylic,
phenolic.
7.3 Showtheproductforthereactionsofafwithhydroxide.
a)
CH3CH2CH2OH
c)
b)CH3CH2CH2Br
e)
OHf)
Br
CH3
d)
CH3 CBr
CH3
CH3
CH3 COH
CH3
7.4GivetheproductsforthereactionsofeachsubstratebelowwithPhMgBr/
H3O ,metachloroperoxybenzoicacid(MCPBA),andHI.
O
OCH3CH3CH=CHCH3
CH3CH2CH2OH
OH
7.6ProblemSet155
7.6 Useanalkoxideandanalkylhalidetopreparetheethersbelow.
b)
a)
O
CH3
CH3
CH3
7.7 ProvidestructuresforthereactionproductsAHbelow.
O
1)CH3CH2MgBr
A PBr3
2)H3O
CH3 1)BH3
C H2SO4
D
2)H2O2,OH
CH3CH2CH2C=O
OH
1)NaBH4
2)HBr
H2SO4
K2CrO4
E
OtertBu
KMnO4
cold